title: 17β-estradiol protects mitochondrial functions through extracellular-signal-regulated kinase in C2C12 muscle cells.
abstract: OBJECTIVE
  We have previously shown that exposure to 17β-estradiol (E2) prior to induction of apoptosis with H2O2 protects skeletal muscle cells against oxidative damage. However, the mechanism involved in the protective action of the hormone is poorly understood. In the present study, we focused on the mechanism by which ERK mediates this survival effect in connection with COXIV activity and mitochondrial membrane potential.
  
  
  METHODS
  Immunocytochemistry, Western blot, cytochrome c oxidase complex IV (COXIV) activity, coimmunoprecipitation and JC-1 dye by flow cytometry were carried out using C2C12 myoblasts as experimental model.
  
  
  RESULTS
  E2 is able to activate ERK and then induces its translocation to mitochondria. Using the pharmacological inhibitor of ERK activation U0126 we show that E2, through ERK activation, is able to enhance COXIV activity. Moreover, the hormone increases the interaction between COXIV and ERK. Also, we found that hydrogen peroxide decreases COXIV activity and that preincubation of the cells with E2 prior to induction of apoptosis prevents this effect. In addition, we observe that the estrogen inhibits the collapse of mitochondrial membrane potential induced by H2O2, involving ERK and COXIV.
  
  
  CONCLUSIONS
  Our data demonstrate that E2 promotes ERK activation and translocation to mitochondria preventing the decline in COXIV activity and in turn, alteration of mitochondrial membrane potential by oxidative stress, in C2C12 myoblasts.
authors.affiliation: Departamento de Biología, Bioquímica & Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Ronda
authors.forename: Andrea
authors.initials: A
authors.lastname: Vasconsuelo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Boland
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects*
chemical_list: D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases